Key result
Doxorubicin decreased H-FABP and BNP protein levels below detection threshold despite unchanged or elevated mRNA expression, an effect not abolished by the proteasome inhibitor bortezomib.
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The abnormal expression of BNP and H-FABP proteins after doxorubicin treatment suggests post-transcriptional interference, making their diagnostic value for anthracycline cardiotoxicity questionable.
The aim of the study was to verify the thesis that the cardiotoxic effects of doxorubicin are connected with activation of the ubiquitin - proteasome pathway followed by protein degradation. The expression of myocardial damage markers - fatty acid binding protein (H-FABP) and brain natriuretic peptide (BNP) was evaluated in rat fetal cardiomyocytes simultaneously treated with doxorubicin and the proteasome inhibitor - bortezomib. The level of H-FABP and BNP protein under the influence of doxorubicin was decreased below the detection threshold with unchanged (H-FABP) or elevated (BNP) mRNA expression level. Against the expectations, the inhibitor of proteasome did not abolish this effect. The observed abnormal expression of BNP and H-FABP protein after doxorubicin treatment makes their diagnostic significance in anthracycline cardiotoxicity questionable.
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Tereszkiewicz et al. (2014) studied Doxorubicin cardiotoxicity. Doxorubicin and Bortezomib vs. Control cells was evaluated on Expression of H-FABP and BNP protein and mRNA. Doxorubicin decreased H-FABP and BNP protein levels below detection threshold despite unchanged or elevated mRNA expression, an effect not abolished by the proteasome inhibitor bortezomib.
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